Regulation of gene expression is a complex phenomenon poorly understood. Our project aims to improve our knowledge about non-coding sequences, increasingly show to be relevant for modulating gene expression, using dystrophin gene and dystrophinopathies as model. Among the series of characterised patients, available in the collaborative units, several have unusual mutations and phenotype suggesting a role of non-coding regions. We will analyse these patients in order to identify and functionally study the regulatory sequences responsible. We will define the intronic breakpoints as well as other non-coding regions involved in dystrophin mutations. We will characterise these sequences by experimental studies to test their regulatory function with particular attention to those involved in pre-mRNA splicing. we will evaluate the feasibility of a targeted modulation of dystrophin gene expression using antisense oligonucleotides.
Funding SchemeCSC - Cost-sharing contracts
2300 RA Leiden